fibroblast growth factor receptor inhibitor
- Previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement.
- Relapsed or refractory myeloid/lymphoid neoplasms with fibroblast growth factor receptor 1 (FGFR1) rearrangement.
FGFR kinase inhibitor that binds to and inhibits FGFR1, FGFR2, and FGFR3 enzyme activity which results in decreased FGFR-related signaling and decreased cell viability in cell lines expressing FGFR genetic alterations, including point mutations, amplifications, and fusions.
Decreased spread of locally advanced or metastatic cholangiocarcinoma and relapsed/refractory myeloid/lymphoid neoplasms.
Absorption: Rapidly absorbed; extent of absorption unknown.
Distribution: Extensively distributed to tissues.
Protein Binding: 90.6%.
Metabolism and Excretion: Primarily metabolized in the liver via CYP3A4 isoenzyme. Primarily excreted in feces (82%; 1.4% unchanged), with 12.6% excreted in urine (1% unchanged).
Half-life: 15.4 hr.
TIME/ACTION PROFILE (plasma concentrations)
|PO||unknown||1.1 hr||24 hr|
- OB: Pregnancy (may cause fetal harm)
- Lactation: Lactation.
Use Cautiously in:
- Severe renal or hepatic impairment (dose ↓ required)
- Rep: Women of reproductive potential and men with female partners of reproductive potential
- Pedi: Safety and effectiveness not established in children.
Adverse Reactions/Side Effects
CV: peripheral edema
Derm: alopecia, dry skin, nail discoloration, nail hypertrophy, nail infection, palmar-plantar erythrodysesthesia syndrome
EENT: dry eyes, retinal pigment epithelial detachment, blurred vision, visual floaters
Endo: hyperglycemia, hypoglycemia
F and E: dehydration, hypercalcemia, hyperkalemia, hyperphosphatemia, hypocalcemia, hypokalemia, hyponatremia, hypophosphatemia
GI: abdominal pain, constipation, diarrhea, dry mouth, hyperbilirubinemia, hypoalbuminemia, ↑ liver enzymes, nausea, stomatitis, vomiting
GU: ↑ serum creatinine, urinary tract infection
Hemat: anemia, leukocytosis, leukopenia, lymphocytopenia, thrombocytopenia
Metabolic: ↓ appetite, ↓ weight, hyperuricemia
MS: arthralgia, fractures
Neuro: dysgeusia, headache
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- Strong CYP3A4 inhibitors, including itraconazole, and moderate CYP3A4 inhibitors may ↑ levels and risk of toxicity; avoid concurrent use, if possible; if must use concurrently, ↓ pemigatinib dose.
- Strong CYP3A4 inducers, including rifampin, and moderate CYP3A4 inducers may ↓ levels and effectiveness; avoid concurrent use.
PO (Adults): 13.5 mg once daily for 14 days, followed by 7 days off of therapy (21-day cycle). Continue 21-day cycles of therapy until disease progression or unacceptable toxicity. Concurrent use of strong or moderate CYP3A4 inhibitors– If previously taking 13.5 mg once daily, ↓ to 9 mg once daily. If previously taking 9 mg once daily, ↓ to 4.5 mg once daily.
PO (Adults): eGFR 15–29 mL/min/1.73 m2 – 9 mg once daily for 14 days, followed by 7 days off of therapy (21-day cycle). Continue 21-day cycles of therapy until disease progression or unacceptable toxicity.
PO (Adults): Severe hepatic impairment (total bilirubin >3x ULN)– 9 mg once daily for 14 days, followed by 7 days off of therapy (21-day cycle). Continue 21-day cycles of therapy until disease progression or unacceptable toxicity.
PO (Adults): 13.5 mg once daily until disease progression or unacceptable toxicity. Concurrent use of strong or moderate CYP3A4 inhibitors– If previously taking 13.5 mg once daily, ↓ to 9 mg once daily. If previously taking 9 mg once daily, ↓ to 4.5 mg once daily.
PO (Adults): eGFR 15–29 mL/min/1.73 m2 – 9 mg once daily until disease progression or unacceptable toxicity.
PO (Adults): Severe hepatic impairment (total bilirubin >3x ULN)– 9 mg once daily until disease progression or unacceptable toxicity.
Tablets: 4.5 mg, 9 mg, 13.5 mg
- Perform comprehensive ophthalmological exam including OCT before starting pemigatinib, every 2 mo for first 6 mo, and every 3 mo thereafter during therapy. If visual symptoms of retinal pigment epithelial detachment (blurred vision, visual floaters, photopsia) occur, refer patient for ophthalmologic evaluation urgently, with follow-up every 3 wk until resolution or discontinuation of pemigatinib. If asymptomatic and stable on serial examination, continue pemigatinib. If symptomatic or worsening on serial examination, hold pemigatinib. If asymptomatic and improved on subsequent examination, resume at a lower dose. If symptoms persist or do not improve, consider permanent discontinuation of pemigatinib.
- Assess for dry eyes. Occurs frequently. Treat with ocular demulcents.
Lab Test Considerations:
Verify a negative pregnancy test before starting therapy.
- Patient selection is based on presence of an FGFR2 fusion or rearrangement as detected by an FDA-approved test. Information is available at http://www.fda.gov/CompanionDiagnostics.
- Monitor for hyperphosphatemia periodically during therapy. Begin a low phosphate diet when serum phosphate level is >5.5 mg/dL. For serum phosphate levels >7 mg/dL-≤10 mg/dL, start phosphate lowering therapy and monitor serum phosphate weekly. If levels ≥7 mg/dL within 2 wk of starting phosphate lowering therapy, hold pemigatinib. When phosphate level <7 mg/dL, resume pemigatinib at same dose for 1st occurrence or at lower doses for subsequent occurrences. If serum phosphate >10 mg/dL, start phosphate lowering therapy and monitor serum phosphate weekly. If levels ≥10 mg/dL within 1 wk after starting phosphate lowering therapy, hold pemigatinib. When phosphate levels <7 mg/dL resume pemigatinib at next lower dose. If serum phosphate levels >10 mg/dL after 2 dose reductions, discontinue pemigatinib permanently.
- May cause ↓ hemoglobin, lymphocytes, platelets and leukocytes and ↑ leukocytes.
- May cause ↑ AST, ALT, alkaline phosphatase, and bilirubin and ↓ albumin.
- May cause ↑ or ↓ calcium, glucose, and potassium, and ↓ sodium.
- May cause ↑ urate and serum creatinine. Within first 21-day cycle serum creatinine increased (mean 0.2 mg/dL) and reached steady state by Day 8 and decreased during 7 days off therapy. If elevations in serum creatinine persist, consider alternate measures of renal function. Calculate CCr using MDRD equation for dose adjustment.
- Recommended dose reductions: Cholangiocarcinoma with FGFR2 Fusion or Rearrangement: 1st reduction: 9 mg once daily for first 14 days of each 21-day cycle 2nd reduction: 4.5 mg once daily for first 14 days of each 21-day cycle 3rd reduction: discontinue. Myeloid/Lymphoid Neoplasms with FGFR1 Rearrangement 1st reduction: 9 mg once daily 2nd reduction: 4.5 mg once daily 3rd reduction: 4.5 mg once daily for first 14 days of each 21-day cycle. Permanently discontinue pemigatinib if unable to tolerate 4.5 mg once daily for 14 days of each 21-day cycle.
- PO Administer once daily at the same time each day, without regard to food. DNC: Swallow tablet whole; do not break, crush, chew, or dissolve.
- Instruct patient to take pemigatinib as directed at same time each day. If patient vomits or dose is missed by ≥4 hr, take next dose at scheduled time. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
- Advise patient to notify health care professional immediately if visual changes (blurred vision, flashes of light, see black spots) or signs and symptoms of hyperphosphatemia (muscle cramps, numbness, tingling around mouth) occur.
- Inform patient that nail disorders and dry eyes may occur. Artificial tear or substitutes and hydrating or lubricating eye gels may be used prevent or treat dry eyes.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
- Rep: May cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception and to avoid breastfeeding during and for 1 wk after last dose.
- Emphasize importance of frequent eye exams and lab test to monitor for side effects.
- Decreased spread of locally advanced or metastatic cholangiocarcinoma.
- Improved blood counts in patients with myeloid/lymphoid neoplasms.